Fetal growth is dependent on the placenta. The mechanisms by which peptide growth factors influence normal trophoblast growth and differentiation are central to this process, as are the pathways that regulate transport of nutrients across the trophoblast. In particular, the amino acid transport function of the placenta is dependent on its state of differentiation, and the mechanisms controlling transport at various stages of trophoblast differentiation have not been defined. One class of peptide growth factors, the insulin-like growth factors (IGF-1 and IGF-2), are likely to play major roles in regulating placental growth, development, and function, and the goals of this project are to elucidate the steps by which the IGFs influence trophoblast proliferation, differentiation, ad nutrient transport. For these studies, normal human trophoblasts and the b30 clone of the human BeWo choriocarcinoma cell line will be used as experimental model systems. Four aims are proposed: 1. To characterize the expression of IGF receptors as a function of trophoblast differentiation. 2. To determine the polarity of receptor expression on maternal- and fetal-facing trophoblast membranes. 3. To define the effects of IGF-1 and IGF-2 on trophoblast proliferation, differentiation, and amino acid transport. 4. To investigate the roles of IGF binding proteins in modulating IGF activity in the differentiating trophoblast. The results of these studies will provide insights into the control of trophoblast growth and development, and will define the steps that are crucial for optimal maternal-fetal exchange of amino acids. These observations should enhance our understanding of the mechanisms regulating fetal growth and thereby contribute to improved strategies to ensure fetal well-being.